DESCRIPTION: Antimicrobial peptides of the human beta-defensin family are recognized as important components of the innate immune responses of oral epithelia and epithelia throughout the body. These peptides may be particularly important in the oral cavity where microbial flora is present in high numbers at all times. The overall working hypothesis for this project is that beta-defensins, and other antimicrobial peptides, aid oral health in two main ways, first, by their direct antimicrobial activity, and second, by their cytokine-like functions to stimulate other cells within the tissue to respond appropriately to the microbial challenge. The goal of this project is to expand previous work on beta-defensin expression and regulation in oral epithelial cells into a more biological framework. While continuing in vitro studies, two model systems, an oral soft tissue model and a tooth pulp model, will be used to investigate the expression of beta-defensins and to explore their role as functional mediators of cell interactions in innate immunity in response to exposure to oral commensal and pathogenic bacteria. The specific hypotheses are 1) that innate immune mechanisms that function within the oral soft tissue are also reflected in the tooth pulp;2) that beta-defensins are expressed in odontoblasts, the epithelial-like cells that serve as the barrier within pulp, 3) that beta-defensins mediate communication between epithelial cells (or odontoblasts) and dendritic cells, the primary cells that bridge innate and adaptive immunity;and 4) that beta-defensins expressed in oral epithelium vs. tooth pulp are different and reflect regional differences in function and interaction between epithelial cells (or odontoblasts) and their respective populations of dendritic cells. These studies will lead to new insights on the role of innate immunity and new potential targets for therapeutic drug development for oral infections.